We have demonstrated that a clinical dose of shock waves (SWs) applied to the lower pole calyx of one kidney as shock wave lithotripsy (SWL) induces a lesion of predictable size and composition, reduces renal blood flow in both kidneys, and produces a renal response the severity of which is related to risk factors. These risk factors include input energy (kilovolt), the SWs, kidney size, number of SWs administered, pre-existing renal inflammation or disease, and SWs applied to both the same kidney during the same treatment session. Since the newer 3rd-generation lithotripters are less effective at breaking stones and appear to be more prone to cause adverse effects than the Donrier HM3 lithotripter, the proposed studies will expand our existing focus to include studies of the new and emerging lithotripters. The goal of such studies is to develop new treatment strategies and technologies with the potential to improve the efficacy and safety of all lithotripters. Aims 1 and 2 will 1) enhance and refine our current view of mechanisms for SW-induced renal injury, 2) determine the possible role of renal vasoconstriction in minimizing the renal trauma caused by SWs, and 3) determine the extent to which prevention of oxidative stress during SWL may minimize or prevent the acute and/or chronic lesions caused by SWs. Aims 3 and 4 will focus on several new risk factors for SWL. These factors include conditions that might be expected to worsen or lessen the tendency for bleeding to occur in renal tissue damaged by shock waves, parameters for administration of SWs, and characteristics of the SW, itself. We will also assess a 3rd-generation lithotripter, the Direx Compact Delta, which tight focal zone and high incident pressure, and an emerging technology in SWL, a twin-head lithotripter, the Duet by Direct their potential to cause renal trauma and impair renal function. All of these proposed studies aim at understanding the adverse effects of shock waves and advancing the safety of all stone patients at a time when reports of adverse effects in SWL are on the rise.